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Attorney General Eric Holder said the Obama administration "strongly opposes" a California ballot measure to legalize marijuana, warning that federal drug-enforcement efforts would be "greatly complicated" if the measure passes.

Recent polls indicate voters narrowly favor passing the Regulate, Control and Tax Cannabis Act, also known as Proposition 19, in next month's election. If passed, the measure would only affect state law, leaving intact the federal law that classifies marijuana as a controlled substance alongside cocaine and other drugs.

Mr. Holder said in a letter Wednesday to nine former Drug Enforcement Administration chiefs that the administration would continue to enforce federal law if California legalizes marijuana. The DEA chiefs had urged him to speak out on the matter.

The ballot measure would block state police officers from seizing marijuana that complies with state law. That would be a "significant impediment" for federal agents, Mr. Holder wrote, because the federal government typically works with local law enforcement when carrying out marijuana and other drug busts.

Already, California has decriminalized possession of smaller quantities of marijuana deemed to be for personal use. The measure would go further than existing law in California and other states that allow use of the drug for medicinal purposes.

The Obama administration has largely hewed to the marijuana-enforcement policy of previous administrations. Mr. Holder has said the government won't target medicinal-marijuana operations that comply with state law, but will continue to pursue prosecutions of traffickers.

Joseph McNamara, a retired San Jose police chief and supporter of Proposition 19, said in response to Mr. Holder's letter that efforts to block marijuana use "waste billions of dollars" and are the wrong priority "in the midst of a sagging economic recovery."

A poll early this month by SurveyUSA found 48% of likely voters support Proposition 19, with 41% opposed. However, the measure is opposed by California lawmakers of both parties, who are likely to step up their campaign in the final weeks.

The former DEA officials said the Justice Department should take legal action to prevent Proposition 19 from becoming law, much as the department has sued to block Arizona's enforcement of a state law that seeks to crack down on illegal immigration. Mr. Holder, in his letter, shied away from that question, saying only that the Justice Department is "considering all available legal and policy options" if the measure passes.

There are some differences in the Arizona and California cases. According to the federal government's legal position—which Arizona is challenging—the Arizona law required state law enforcement to take action that infringed on federal immigration responsibilities. The California measure, by contrast, would merely result in the state withholding its assistance on federal marijuana drug enforcement.